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Response of the μ-opioid system to social rejection and acceptance

Molecular Psychiatry volume 18, pages 1211–1217 (2013)Cite this article

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Abstract

The endogenous opioid system, which alleviates physical pain, is also known to regulate social distress and reward in animal models. To test this hypothesis in humans (n=18), we used an μ-opioid receptor (MOR) radiotracer to measure changes in MOR availability in vivo with positron emission tomography during social rejection (not being liked by others) and acceptance (being liked by others). Social rejection significantly activated the MOR system (i.e., reduced receptor availability relative to baseline) in the ventral striatum, amygdala, midline thalamus and periaqueductal gray (PAG). This pattern of activation is consistent with the hypothesis that the endogenous opioids have a role in reducing the experience of social pain. Greater trait resiliency was positively correlated with MOR activation during rejection in the amygdala, PAG and subgenual anterior cingulate cortex (sgACC), suggesting that MOR activation in these areas is protective or adaptive. In addition, MOR activation in the pregenual ACC was correlated with reduced negative affect during rejection. In contrast, social acceptance resulted in MOR activation in the amygdala and anterior insula, and MOR deactivation in the midline thalamus and sgACC. In the left ventral striatum, MOR activation during acceptance predicted a greater desire for social interaction, suggesting a role for the MOR system in social reward. The ventral striatum, amygdala, midline thalamus, PAG, anterior insula and ACC are rich in MORs and comprise a pathway by which social cues may influence mood and motivation. MOR regulation of this pathway may preserve and promote emotional well being in the social environment.

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Acknowledgements

This research was supported by National Institute of Health Grants K01 MH085035 (DTH), K23 MH074459 (SAL), R01 DA022520 and R01 DA027494 (JKZ), a National Alliance for Research on Schizophrenia and Depression Young Investigator Award (DTH), pilot grants from the Michigan Institute for Clinical and Health Research (DTH), a Rachel Upjohn Clinical Scholars Award (DTH) and the Phil F Jenkins Foundation (JKZ).

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  1. Department of Psychiatry, The Molecular and Behavioral Neuroscience Institute, University of Michigan, Ann Arbor, MI, USA

    D T Hsu, B J Sanford, K K Meyers, T M Love, H Wang, L Ni, B J Mickey, S T Korycinski, S A Langenecker & J-K Zubieta

  2. Department of Psychology, Marquette University, Milwaukee, WI, USA

    K E Hazlett

  3. Department of Psychiatry, Oregon Health and Science University, Portland, OR, USA

    S J Walker

  4. Department of Radiology, University of Michigan, Ann Arbor, MI, USA

    R A Koeppe & J-K Zubieta

  5. Department of Psychology, Ohio State University, Columbus, OH, USA

    J K Crocker

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Dr RAK is a consultant for Avid Corp., Merck, and Johnson & Johnson; Dr BJM received salary support from St Jude Medical for research unrelated to this manuscript; Dr SAL received compensation for consulting to CogState Limited unrelated to this manuscript. All the other authors declare no conflict of interest.

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Hsu, D., Sanford, B., Meyers, K. et al. Response of the μ-opioid system to social rejection and acceptance. Mol Psychiatry 18, 1211–1217 (2013). https://doi.org/10.1038/mp.2013.96

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